Executive summary: Quality standards of care units for people with sexual and gender diversity.

Comprehensive biopsychosocial care for people with gender incongruence (ICD 11) who are transgender (trans) or gender diverse is a complex process in which the quality of the medical transition can only be guaranteed after a multidisciplinary approach, through teams that integrate professionals with training and experience not only in medicine but also in diversity and gender identity. Based on this, the Gonad, Identity and Sexual Differentiation working group of the Spanish Society of Endocrinology and Nutrition (GT-GIDSEEN) has established minimum care requirements that aim to guarantee adequate health care for these people by professionals. A position paper has been produced and is available at https://www.seen.es/portal/documentos/estandares-calidad-gidseen-2024.

A Systematic Review on the Reinforcement Loop in Aesthetic Medicine and Surgery: The Interplay of Social Media, Self-Perception, and Repeat Procedures.

INTRODUCTION: This systematic review delves into the impact of social media on self-perception and the escalating interest in clinical aesthetic procedures, proposing that social media significantly influences beauty standards and increases demand for aesthetic enhancements. METHOD: Following PRISMA guidelines, a mixed-method analysis of 34 articles was conducted, sourced from various databases, focusing on social media's psychological effects on clinical aesthetics decisions. The studies encompassed a broad spectrum, including qualitative, quantitative, and mixed methodologies, reflecting diverse geographical and cultural perspectives. RESULTS: The quantitative analysis demonstrated a strong positive correlation between social media usage and the consideration of aesthetic procedures (r=0.45, p<0.001), indicating a significant impact. Specific findings included a large effect size (Cohen's d=0.8) for the relationship between time spent on social media and the desire for aesthetic enhancements. Individuals spending more than 3 hours per day on social media platforms were twice as likely to consider aesthetic procedures compared to those with less usage, with a 95% confidence interval indicating robustness in these findings. CONCLUSION: Confirming the reinforcing effect of social media on aesthetic decision-making, this study highlights the complex interplay between digital media exposure, altered self-perception, and the increased inclination towards aesthetic procedures. It suggests a critical need for practitioners to carefully navigate the digital influence on patient's desires, reinforcing the significance of understanding psychological motivations and societal pressures in clinical aesthetics. This comprehensive analysis offers pivotal insights for clinical practice and ongoing research into social media's role in contemporary beauty standards. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Harnessing extracellular vesicle membrane for gene therapy: EVs-biomimetic nanoparticles.

One of the main concerns in oligonucleotide-based therapeutics is achieving a successful cell targeting while avoiding drug degradation and clearance. Nanoparticulated drug delivery systems have emerged as a way of overcoming these issues. Among them, membrane-coated nanoparticles are of increasing relevance mainly due to their enhanced cellular uptake, immune evasion and biocompatibility. In this study, we designed and elaborated a simple and highly tuneable biomimetic drug delivery nanosystem based on a polymeric core surrounded by extracellular vesicles (EVs)-derived membranes. This strategy should allow the nanosystems to benefit from the properties conferred by the membrane proteins present in EVs membrane, key paracrine mediators. The developed systems were able to successfully encapsulate the required oligonucleotides. Also, their characterisation through already well standardised methods (dynamic light scattering, transmission electron microscopy and nanoparticle tracking analysis) and by fluorescence cross-correlation spectroscopy (FCCS) showed the desired core-shell structure. The cellular uptake using different cell types further confirmed the coating though an enhancement in cell internalisation of the developed biomimetic nanoparticles. This study brings up new possibilities for GapmeR delivery as it might be a base for the development of new delivery systems for gene therapy.

Influence of lower limb isokinetic muscle strength and power on the occurrence of falls in community-dwelling older adults: A longitudinal study.

INTRODUCTION: Previous studies have highlighted the association between lower limb muscle strength and falls in older adults. However, a comprehensive understanding of the specific influence of each lower limb muscle group on fall occurrences remains lacking. OBJECTIVE: This study aimed to investigate the impact of knee, ankle, and hip muscle strength and power on falls in older adults, with the goal of identifying which muscle groups are more predictive of fall risk in this population. METHODS: This longitudinal observational study enrolled 94 community-dwelling older adults. Muscle strength and power of the ankle's plantiflexors and dorsiflexors, knee flexors and extensors, and hip flexors, extensors, adductors, and abductors were assessed using a Biodex System 4 Pro® isokinetic dynamometer. Fall occurrences were monitored through monthly telephone contact over a year. RESULTS: Participants, with a median age of 69 years (range 64-74), included 67% women, and 63.8% reported a sedentary lifestyle. Among them, 45,7% of older adults were classified as fallers. Comparative analyses revealed that non-fallers displayed significantly superior isokinetic muscle strength in the hip abductors and adductors, along with higher muscle power in the hip abductors, hip flexors, and knee flexors compared to fallers. Multivariate logistic regression analysis indicated that a 1 Nm/Kg increase in hip abductor strength reduced the chance of a fall by 86.3%, and a 1 Watt increase in hip flexor power reduced the chance of a fall by 3.6%. CONCLUSION: The findings indicate that hip abductor strength and hip flexor power can be considered protective factors against falls in independent older adults in the community. These findings may contribute to developing effective fall-prevention strategies for this population.

Magnification in preclinical procedures: effect on muscle activity and angular deviations of the neck and trunk.

Objectives: This study aimed to assess the effects of different magnification systems on the angular deviations of the neck and trunk and the muscle activities of the upper back and neck during preclinical cavity preparation. Methods: This was an experimental laboratory study, with the angular deviations from the neutral positions of the neck and trunk and the activities of the bilateral upper back (the descending and ascending trapezius) and neck (sternocleidomastoid) muscles as the dependent variables. The independent variables were the different magnification systems used (Simple, Galilean, and Keplerian loupes, with direct vision as the control) and prepared teeth (teeth 16, 26, 36, and 46). A dental mannequin phantom head with artificial resin teeth was used, and Class I cavity preparations for composite resin were performed on teeth 16, 26, 36, and 46 using a 1012 round diamond bur at low speed. To analyze the angular deviations, the postures adopted during the procedure were recorded using a tripod-mounted camera positioned to provide a lateral view of the operator. A trained researcher measured the angular deviations using the software entitled "Software for Postural Assessment"-SAPO (version 0.69). Bilateral muscle activity was assessed using surface electromyography. Descriptive statistical analysis was performed, and after verifying the assumptions of normality and homoscedasticity, two-way analysis of variance and the Tukey and Games-Howell post-hoc tests were used to compare the data (α=0.05). Results: The angular deviation from the neutral position of the neck was found to be significantly higher during cavity preparations performed with the naked eye and the Simple loupe, irrespective of the prepared tooth. With regard to tooth location, the angular deviation of the neck was significantly greater during cavity preparation on teeth 16 and 26, and the angular deviation of the trunk was significantly greater during cavity preparation on tooth 26, regardless of the magnification system used. There were significant differences in right sternocleidomastoid muscle activity between the Simple, Galilean, and Keplerian loupes, with activity being the lowest for the Galilean loupe (p = 0.008). There were no significant differences in left sternocleidomastoid muscle activity between the loupes, regardless of the prepared tooth (p = 0.077). The activities of the bilateral descending trapezius and the right ascending trapezius muscles were significantly lower when the Galilean loupe was used (p < 0.010). Conclusion: These results suggest that the Galilean loupe resulted in lower muscle activity in the neck and back regions and that the Galilean and Keplerian loupes resulted in less angular deviations of the neck and trunk during cavity preparation.

Genomic characterisation of the population structure and antibiotic resistance of Salmonella enterica serovar Infantis in Chile, 2009-2022.

Background: Multidrug-resistant (MDR) Salmonella Infantis has disseminated worldwide, mainly linked to the consumption of poultry products. Evidence shows dissemination of this pathogen in Chile; however, studies are primarily limited to phenotypic data or involve few isolates. As human cases of Salmonella Infantis infections have substantially increased in recent years, this study aimed to characterise the genomic epidemiology and antimicrobial-resistance profiles of isolates obtained from different sources, aiming to inform effective surveillance and control measures. Methods: We sequenced 396 Salmonella Infantis genomes and analysed them with all publicly available genomes of this pathogen from Chile (440 genomes in total), representing isolates from environmental, food, animal, and human sources obtained from 2009 to 2022. Based on bioinformatic and phenotypic methods, we assessed the population structure, dissemination among different niches, and antimicrobial resistance (AMR) profiles of Salmonella Infantis in the country. Findings: The genomic and phylogenetic analyses showed that Salmonella Infantis from Chile comprised several clusters of highly related isolates dominated by sequence type 32. The HC20_343 cluster grouped an important proportion of all isolates. This was the only cluster associated with pESI-like megaplasmids, and up to 12 acquired AMR genes/mutations predicted to result in an MDR phenotype. Accordingly, antimicrobial-susceptibility testing revealed a strong concordance between the AMR genetic determinants and their matching phenotypic expression, indicating that a significant proportion of HC20_343 isolates produce extended-spectrum ß-lactamases and have intermediate fluoroquinolone resistance. HC20_343 Salmonella Infantis were spread among environmental, animal, food, and human niches, showing a close relationship between isolates from different years and sources, and a low intra-source genomic diversity. Interpretation: Our findings show a widespread dissemination of MDR Salmonella Infantis from the HC20_343 cluster in Chile. The high proportion of isolates with resistance to first-line antibiotics and the evidence of active transmission between the environment, animals, food, and humans highlight the urgency of improved surveillance and control measures in the country. As HC20_343 isolates predominate in the Americas, our results suggest a high prevalence of ESBL-producing Salmonella Infantis with intermediate fluoroquinolone resistance in the continent. Funding: Partially supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services as part of an award, FDU001818, with 30% percent funded by FDA/HHS; and by Agencia de Investigación y Desarrollo de Chile (ANID) through FONDECYT de Postdoctorado Folio 3230796 and Folio 3210317, FONDECYT Regular Folio 1231082, and ANID-Millennium Science Initiative Program-ICN2021_044.

Clinical Trials That Have Changed Clinical Practice and Care of Pregnant People With HIV.

Over the last 4 decades, significant advances in the care of HIV during pregnancy have successfully reduced, and nearly eliminated, the risk of perinatal HIV transmission. The baseline risk of transmission without intervention (25% to 30%) is now <1% to 2% in the United States with contemporary antepartum, intrapartum, and postnatal interventions. In this review, we discuss 3 landmark clinical trials that substantially altered obstetric practice for pregnant individuals with HIV and contributed to this extraordinary achievement: 1) the Pediatric AIDS Clinical Trials Group 076 Trial determined that antepartum and intrapartum administration of antiretroviral drug zidovudine to the pregnant individual, and postnatally to the newborn, could reduce the risk of perinatal transmission by approximately two-thirds; 2) the European Mode of Delivery Collaboration Trial demonstrated performance of a prelabor cesarean birth before rupture of membranes among pregnant people with viremia reduced the risk of perinatal transmission compared with vaginal birth; and 3) the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 Trial identified that dolutegravir-containing, compared with efavirenz-containing, antiretroviral regimens during pregnancy achieved a significantly higher rate of viral suppression at delivery with shorter time to viral suppression, with fewer adverse pregnancy outcomes. Collectively, these trials not only advanced obstetric practice but also advanced scientific understanding of the timing, mechanisms, and determinants of perinatal HIV transmission. For each trial, we will describe key aspects of the study protocol and outcomes, insights gleaned about the dynamics of perinatal transmission, how each study changed clinical practice, and relevant updates to current practice since the trial's publication.

HIV Diagnostics and Vaccines: It Takes Two to Tango.

Current serological tests for HIV screening and confirmation of infection present challenges to the adoption of HIV vaccines. The detection of vaccine-induced HIV-1 antibodies in the absence of HIV-1 infection, referred to as vaccine-induced seropositivity/seroreactivity, confounds the interpretation of test results, causing misclassification of HIV-1 status with potential affiliated stigmatization. For HIV vaccines to be widely adopted with high community confidence and uptake, tests that are agnostic to vaccination status (i.e., only positive for true HIV-1 infection) of tested individuals are needed. Successful development and deployment of such tests will require HIV vaccine developers to work in concert with diagnostic developers. Such tests will need to match today's high-performance standards (accuracy, cost-effectiveness, simplicity) for use in both vaccinated and unvaccinated populations, especially in low- and middle-income countries with high HIV burden. Herein, we discuss the challenges and strategies for developing modified serological HIV tests for concurrent deployment with HIV vaccines.

Use of a footstool improves rectal balloon expulsion in some patients with defecatory disorders.

BACKGROUND: Whether patients with defecatory disorders (DDs) with favorable response to a footstool have distinctive anorectal pressure characteristics is unknown. We aimed to identify the clinical phenotype and anorectal pressure profile of patients with DDs who benefit from a footstool. METHODS: This is a retrospective review of patients with high resolution anorectal manometry (HR-ARM) and balloon expulsion test (BET) from a tertiary referral center. BET was repeated with a 7-inch-high footstool in those who failed it after 120 s. Data were compared among groups with respect to BET results. KEY RESULTS: Of the 667 patients with DDs, a total of 251 (38%) had failed BET. A footstool corrected BET in 41 (16%) of those with failed BET. Gender-specific differences were noted in anorectal pressures, among patients with and without normal BET, revealing gender-based nuances in pathophysiology of DDs. Comparing patients who passed BET with footstool with those who did not, the presence of optimal stool consistency, with reduced instances of loose stools and decreased reliance on laxatives were significant. Additionally, in women who benefited from a footstool, lower anal pressures at rest and simulated defecation were observed. Independent factors associated with a successful BET with a footstool in women included age <50, Bristol 3 or 4 stool consistency, lower anal resting pressure and higher rectoanal pressure gradient. CONCLUSION & INFERENCES: Identification of distinctive clinical and anorectal phenotype of patients who benefited from a footstool could provide insight into the factors influencing the efficacy of footstool utilization and allow for an individualized treatment approach in patients with DDs.

Artificial Intelligence-Generated Draft Replies to Patient Inbox Messages.

Importance: The emergence and promise of generative artificial intelligence (AI) represent a turning point for health care. Rigorous evaluation of generative AI deployment in clinical practice is needed to inform strategic decision-making. Objective: To evaluate the implementation of a large language model used to draft responses to patient messages in the electronic inbox. Design, Setting, and Participants: A 5-week, prospective, single-group quality improvement study was conducted from July 10 through August 13, 2023, at a single academic medical center (Stanford Health Care). All attending physicians, advanced practice practitioners, clinic nurses, and clinical pharmacists from the Divisions of Primary Care and Gastroenterology and Hepatology were enrolled in the pilot. Intervention: Draft replies to patient portal messages generated by a Health Insurance Portability and Accountability Act-compliant electronic health record-integrated large language model. Main Outcomes and Measures: The primary outcome was AI-generated draft reply utilization as a percentage of total patient message replies. Secondary outcomes included changes in time measures and clinician experience as assessed by survey. Results: A total of 197 clinicians were enrolled in the pilot; 35 clinicians who were prepilot beta users, out of office, or not tied to a specific ambulatory clinic were excluded, leaving 162 clinicians included in the analysis. The survey analysis cohort consisted of 73 participants (45.1%) who completed both the presurvey and postsurvey. In gastroenterology and hepatology, there were 58 physicians and APPs and 10 nurses. In primary care, there were 83 physicians and APPs, 4 nurses, and 8 clinical pharmacists. The mean AI-generated draft response utilization rate across clinicians was 20%. There was no change in reply action time, write time, or read time between the prepilot and pilot periods. There were statistically significant reductions in the 4-item physician task load score derivative (mean [SD], 61.31 [17.23] presurvey vs 47.26 [17.11] postsurvey; paired difference, -13.87; 95% CI, -17.38 to -9.50; P < .001) and work exhaustion scores (mean [SD], 1.95 [0.79] presurvey vs 1.62 [0.68] postsurvey; paired difference, -0.33; 95% CI, -0.50 to -0.17; P < .001). Conclusions and Relevance: In this quality improvement study of an early implementation of generative AI, there was notable adoption, usability, and improvement in assessments of burden and burnout. There was no improvement in time. Further code-to-bedside testing is needed to guide future development and organizational strategy.

Predictors of the Outcome at 2 Years in Neonates With Congenital Cytomegalovirus Infection.

BACKGROUND: Approximately 20% of neonates with congenital cytomegalovirus (cCMV) develop long-term sequelae. The ability to accurately predict long-term outcomes as early as the neonatal period would help to provide for appropriate parental counseling and treatment indications. With this study, we aimed to identify neonatal predictive markers of cCMV long-term outcomes. METHODS: As this study's subjects, we chose neonates diagnosed with cCMV in 13 hospitals throughout France recruited from 2013 to 2017 and evaluated for at least 2 years with thorough clinical, audiology, and imaging evaluations and psychomotor development tests. RESULTS: A total of 253 neonates were included, and 3 were later excluded because of the identification of a genetic disorder. A total of 227 were followed up for 2 years: 187/227 (82%) and 34/227 (15%) were infected after a maternal primary or nonprimary infection, respectively, 91/227 (40%) were symptomatic at birth, and 44/227 (19%) had cCMV sequelae. Maternal primary infection in the first trimester was the strongest prognosis factor (odds ratio = 38.34 [95% confidence interval, 5.02-293], P < .001). A predictive model of no risk of sequelae at 2 years of age according to normal hearing loss at birth, normal cerebral ultrasound, and normal platelet count had 98% specificity, 69% sensitivity, and 0.89 area under the curve (95% confidence interval, 0.83-0.96). CONCLUSIONS: In the studied population, children with normal hearing at birth, normal platelet count at birth, and a normal cranial ultrasound had no risk of neurologic sequelae and a low risk of delayed unilateral sensorineural hearing loss. The use of this model based on readily available neonatal markers should help clinicians establish a personalized care pathway for each cCMV neonate.

An Emergent Change in Epidemiologic and Microbiological Characteristics of Bloodstream Infections in Adults With Febrile Neutropenia Resulting From Chemotherapy for Acute Leukemia and Lymphoma at Reference Centers in Chile, Ecuador, and Peru.

Background: Febrile neutropenia is a life-threatening condition commonly observed in patients with hematologic malignancies. The aim of this article is to provide updated knowledge about bloodstream infections in febrile neutropenia episodes within the Andean region of Latin America. Method: This retrospective study was based in 6 hospitals in Chile, Ecuador, and Peru and included adult patients with acute leukemia or lymphoma and febrile neutropenia between January 2019 and December 2020. Results: Of the 416 febrile neutropenia episodes, 38.7% had a bloodstream infection, 86% of which were caused by gram-negative rods, with Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa being the most frequently identified bacteria. K pneumoniae isolates were more frequently resistant than E coli to cefotaxime (65% vs 39.6%), piperacillin-tazobactam (56.7% vs 27.1%), and imipenem (35% vs 2.1%) and were more frequently multidrug resistant (61.7% vs 12.5%). Among P aeruginosa, 26.7% were resistant to ceftazidime, piperacillin-tazobactam, and imipenem, and 23.3% were multidrug resistant. Overall 30-day mortality was 19.8%, being higher with vs without a bloodstream infection (26.7% vs 15.3%, P = .005). Fever duration was also significantly longer, as well as periods of neutropenia and length of hospital stay for patients with bloodstream infection. Additionally, the 30-day mortality rate was higher for episodes with inappropriate vs appropriate empirical antibiotic therapy (41.2% vs 26.6%, P = .139). Conclusions: Considering the high rates of bacteria-resistant infection and 30-day mortality, it is imperative to establish strategies that reduce the frequency of bloodstream infections, increasing early identification of patients at higher risks of multidrug bacteria resistance, and updating existing empirical antibiotic recommendations.

Pathogenic effects of Leu200Pro and Arg387His VRK1 protein variants on phosphorylation targets and H4K16 acetylation in distal hereditary motor neuropathy.

Rare recessive variants in the human VRK1 gene are associated with several motor neuron diseases (MND), such as amyotrophic lateral sclerosis, spinal muscular atrophy, or distal hereditary motor neuropathies (dHMN). A case with dHMN carrying two novel VRK1 gene variants, expressing Leu200Pro (L200P) and Arg387His (R387H) variant proteins, identified that these protein variants are functionally different. The Leu200Pro variant shares with several variants in the catalytic domain the loss of the kinase activity on different substrates, such as histones, p53, or coilin. However, the distal Arg387His variant and the distal Trp375* (W375X) chinese variant, both located at the end of the low complexity C-terminal region and proximal to the termination codon, retain their catalytic activity on some substrates, and mechanistically their functional impairment is different. The L200P variant, as well as most VRK1 pathogenic variants, impairs the phosphorylation of BAF and histone H4K16 acetylation, which are required for DNA attachment to the nuclear envelope and chromatin accessibility to DNA repair mechanisms, respectively. The R387H variant impairs phosphorylation of H2AX, an early step in different types of DNA damage responses. The functional variability of VRK1 protein variants and their different combinations are a likely contributor to the clinical phenotypic heterogeneity of motor neuron and neurological diseases associated with rare VRK1 pathogenic variants. KEY MESSAGES: VRK1 variants implicated in motor neuron diseases are functionally different. The L200P variant is kinase inactive, and the R387H variant is partially active. VRK1 variants alter H4K16 acetylation and loss of coilin and BAF phosphorylation. VRK1 variants alter Cajal bodies and DNA damage responses. VRK1 variant combination determines the neurological phenotype heterogeneity.

Histological evidence of hypothyroidism in mice chronically exposed to conventional farming.

Worldwide, disorders of the thyroid gland are a growing concern; such can be caused by exposure to contaminants, including agrochemicals used in conventional agriculture, which act as endocrine disruptors. The purpose of this study is to evaluate whether or not exposure to an environment with conventional agriculture leads to thyroid disruption. Mus musculus were used as bioindicator species, captured in two sites: a farm where conventional agriculture is practiced, and a place without agriculture. Thyroid histomorphometric and morphologic data were analyzed. The impacts of the agricultural environment over the thyroid were revealed, as indications of hypothyroidism were observed in exposed mice: the area and volume of epithelial cells were much lower. Alterations in thyroid histomorphology were also observed: lower follicular sphericity, irregularly delimited epithelium and increased exfoliation into the colloid. These results highlight the need for transition from current conventional agricultural systems towards organic systems.